The Generalized Quantitative Model of antibody homeostasis: maintenance of global antibody equilibrium by effector functions

Abstract

The homeostasis of antibodies can be characterized as a balanced production, binding and elimination regulated by an interaction network, which controls B-cell development and selection. Recently we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network.\n\nHere we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody and free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]=KO_SCPCAPDC_SCPCAP. This zone corresponds to the biologically relevant KO_SCPCAPDC_SCPCAP range of reversible interactions. We show that thermodynamic and kinetic properties of antibody-antigen interactions correlate with immunological functions. The formation of stable, long-lived immune complexes correspond to a decrease of entropy and is a prerequisite for the generation of higher order complexes. As the energy of formation of complexes increases we observe a gradual shift from silent clearance to inflammatory reactions. These rules can also be applied to complement activation-related processes, linking innate and adaptive humoral responses. Affinity of the receptors mediating effector functions shows a corresponding range of affinities, allowing the continuous sampling of antibody-bound antigen over the complete range of concentrations. The generation of multivalent, multicomponent complexes triggers effector functions by cross-linking these receptors on effector cells with increasing enzymatic degradation potential.\n\nThus, antibody homeostasis is a thermodynamic system with complex network properties, nested into the host organism by proper immunoregulatory and effector pathways. Maintenance of global antibody equilibrium is achieved by innate qualitative signals modulating a quantitative adaptive immune system, which regulates molecular integrity of the host by tuning the degradation and recycling of molecules from silent removal to inflammatory elimination.